First published September 27, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004568

Ronald B. Postuma

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

From the Department of Neurology, Montreal General Hospital (R.B.P., A.P.), and Department of Epidemiology and Biostatistics (L.J.), McGill University, Montreal; Department of Neurology (J.A., A.B., D.H.), University of Manitoba, Winnipeg, Canada; Pontifical Catholic University of Parana (M.M., A.M.), Curitiba, Brazil; Department of Neurology (D.G.), Ottawa Hospital, University of Ottawa Brain and Mind Research Institute; Department of Neurology (S.F.), University of Calgary; Division of Neurology (R.P.M., A.E.L.), Toronto Western Hospital; and Department of Medicine, Division of Neurology, Djavad Mowafaghian Centre for Brain Health, and Pacific Parkinson's Research Centre (S.A.-C.), University of British Columbia, Vancouver, Canada.

Results: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups −0.48 [95% confidence interval −3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).

Conclusion: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.

Clinicaltrials.gov identifier: NCT01738178.

Classification of evidence: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

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